Severe pegaspargase hypersensitivity reaction rates (grade 3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children's oncology group (COG) clinical trials

PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence ranging 3-41%. We evaluated grade 3 HSRs when given IM vs. IV on six Children's Oncology Group (COG) leukemia trials (2003-2015) to determine differences in HSR rates. 54,280 doses were administered to 16,534 patients. Considering all doses of pegaspargase during induction, consolidation, and delayed intensification, grade 3 HSR rate with IM injection was 5.4% (n=482/8981) compared to 3.2% for IV (n=245/7553) (p<.0001). If only the second and third doses of pegaspargase were analyzed, where the majority of grade 3 HSRs occur, the rate following IM injection was 10.1% (n=459/4534) compared to 5.0% (n=222/4443) for IV (p<.0001). On standardized treatment protocols conducted by the COG during 2003-2015, grade 3 HSR rates to pegaspargase occurred less frequently with IV infusion than IM injection.